Generic Name: Brinzolamide
Brand Name: Azopt

Brinzolamide is a carbonic anhydrase inhibitor formulated for topical ophthalmic use.

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II), found primarily in red blood cells (RBC's), but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP).

Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its high affinity for CA-II, brinzolamide distributes extensively into the RBCs and exhibits a long half-life in whole blood (approximately 111 days). In humans, the metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs. This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are low and generally below assay quantitation limits (<10 ng/mL). Binding to plasma proteins is not extensive (about 60%). Brinzolamide is eliminated predominantly in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with trace concentrations (<1% of the dose) of the N-desmethoxypropyl and O-desmethyl metabolites.

Patients who are hypersensitive to any component of this product.

Brinzolamide has not been studied in patients with severe renal impairment (CrCl <30 mL/min). Because brinzolamide and its metabolite are excreted predominantly by the kidney, brinzolamide is not recommended in such patients.

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and brinzolamide. The concomitant administration of brinzolamide and oral carbonic anhydrase inhibitors is not recommended.

Brinzolamide is a sulfonamide and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of brinzolamide. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may occur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Brinzolamide has not been studied in patients with acute angle-closure glaucoma.

Brinzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

The preservative in AZOPT ophthalmic suspension, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of brinzolamide suspension but may be reinserted 15 minutes after instillation.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from brinzolamide suspension, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15 mg/kg/day (312 times the recommended human ophthalmic dose) were seen during lactation. No other effects were observed. However, following oral administration of ¹⁴C-brinzolamide to lactating rats, radioactivity was found in milk at concentrations below those in the blood and plasma.